crossing96/oncoscreening huggingface dataset:
Efficient Training Corpus Retrieval for Large Language Model Fine Tuning: A Case Study in Cancer.	The objective is to create an automated knowledge extraction tool for cancer research that builds high-quality academic corpora for LLM fine-tuning while investigating its effectiveness in interleukin-6 and bladder cancer domains. To address the current gap in knowledge retrieval techniques for cancer research data collection, we propose KnowledgePipeline, a novel automated tool that incorporates diverse aspects of academic papers and metadata. Our tool integrates content, co-citations, and co-authorship networks to construct domain-specific academic corpora suitable for fine-tuning LLMs. We leverage two LLMs (GPTJ-6.7B and Galactica30B) trained on domain-specific question-answer pairs from the refined data. The system's evaluation focuses on both the quality of extracted knowledge and the performance of fine-tuned models in open-ended question-answering tasks. We see that KnowledgePipeline offers a scalable, automated framework for domain-specific knowledge retrieval and fine-tuned applications in cancer research, advancing literature discovery and addressing critical biomedical challenges. It achieved high relevance scores of 68% for IL-6 and 74.5% for bladder cancer, with a fine-tuned Galactica-30B model demonstrating promising capabilities.	bladder
Prognostic Factors of Long-Term Survival in Non-Muscle-Invasive Bladder Cancer: An 18-Year Retrospective Study from Real-Life Practice.	Introduction: Non-muscle-invasive bladder cancer (NMIBC) is common and heterogeneous, requiring risk-adapted therapeutic strategies. BCG remains standard for intermediate- and high-risk forms, but its effectiveness is influenced by limited access, variable tolerance, treatment resistance, and healthcare system disruptions. Material and Methods: This retrospective study aimed to identify prognostic factors for survival with an additional assessment of the influence of the COVID-19 pandemic. Although we could not directly evaluate the effect of COVID- 19 pandemic due to lack of recorded variables,we hypothesize it may have contributed to the limited impact of BCG therapy in our real-world setting. A total of 100 patients were selected from an initial group of 297 diagnosed in the Urology Clinic of Tg.Mures between 2006 - 2008, followed up until 2024. Prognostic analysis included clinical variables, RecScore and ProgScore were calculated using the EORTC risk calculator. No specific cut-offs were applied; the scores were analyzed as continuous variables. Results: Age over 70 and tumor multiplicity were significantly associated with increased mortality. RecScore was significantly correlated with the risk of relapse (p=0.0464). ProgScore showed a marginal association with mortality in univariate analysis (p=0.0561), but was not significant in multivariate models (p=0,9159). BCG therapy had a marginal protective effect, but did not significantly influence survival. Although we could not directly evaluate the effect of COVID-19 pandemic due to lack of recorded variables,we hypothesize that it may have contributed to treatment discontinuities in this real-life cohort. Conclusions: The results support the need for personalized, risk-based strategies and underline the importance of integrating real-world data into NMIBC management, especially in the context of systemic disruptions.	bladder
FOXA2 promotes glutamine metabolism to facilitate the malignant development of bladder cancer by transcriptionally increasing GLS1 expression.	BACKGROUND: Forkhead box A2 (FOXA2) is found to be abnormally overexpressed in bladder cancer (BCa), but its role and underlying molecular mechanisms in BCa progression remain revealed. METHODS: The expression levels of FOXA2, glutaminase 1 (GLS1), glutamine metabolism-related markers were examined using qRT-PCR and western blot. Glutamine metabolism was assessed by detecting glutamine uptake, intracellular glutamate, ATP, GSH and ROS levels. BCa cell proliferation, migration and invasion were analyzed by CCK8 assay, EdU assay, wound healing assay, and Transwell assay. The regulation of FOXA2 on GLS1 promoter was confirmed by dual-luciferase reporter assay and ChIP assay. Mice xenograft tumor models were constructed to evaluate the role of FOXA2 in BCa tumorigenesis. RESULTS: FOXA2 expression was upregulated in BCa cells and its knockdown significantly decreased GLS1 expression. Silencing of FOXA2 inhibited BCa cell glutamine metabolism, thus suppressing cell proliferation and metastasis, and these effects were reversed by GLS1 overexpression. In terms of mechanism, FOXA2 increased the transcription and expression of GLS1 by binding to its promoter region. Animal study revealed that FOXA2 interference also reduced BCa tumorigenesis through decreasing GLS1 expression. CONCLUSION: FOXA2 accelerated BCa cell proliferation and metastasis by promoting GLS1-mediated glutamine metabolism, providing a novel therapy target for BCa.	bladder
Multi-omics profiling identifies ESM1 as a key mediator of immunoevasion through the SPP1 pathway in bladder cancer.	To investigate the predictive value of Endothelial cell-specific molecule 1 (ESM1) assay for early diagnosis and treatment of bladder cancer (BC) patients. In this study, 1558 clinical samples were included to explore the differential expression of ESM1 mRNA in BC, and in-house samples (n = 195) were collected for immunohistochemistry experiments to validate at the ESM1 protein level. ChIP-Seq, ATAC-seq, and histone modification data were integrated by Cistrome Data Browser to resolve the epigenetic regulatory mechanisms of ESM1. Single-cell sequencing analysis was used to mine the differential expression and intercellular communication of ESM1 at the cellular level. Further, GSEA and STRING were used to construct a PPI network and combined with Cytospace to mine Hub genes to reveal the immune-related pathways involved in ESM1. The potential of ESM1 in immune prediction was assessed by single sample gene set enrichment analysis. Prediction of upstream miRNAs targeting ESM1 (e.g.,miR-129-5p) and construction of regulatory networks. ESM1 protein and mRNA expression in BC tissues was significantly higher than that in normal tissues (p < 0.05), and its transcription was regulated by three major transcription factors as well as enhancers, promoters, and silencers. ESM1 was highly expressed in lymphatic endothelial cells, it participated in the SPP1 signalling pathway, which mediated immune escape and metastasis in BC. High ESM1 expression inhibited both the T-cell receptor and the Fc gamma R-mediated immune pathways and was associated with reduced tumour microenvironment scores, increased tumour purity and reduced immune cell infiltration (p < 0.05). Clinical analysis showed that ESM1 expression was significantly associated with age, ethnicity and clinical stage (p < 0.05) and was effective in differentiating cancerous tissues (AUC = 0.94). In addition, miR-129-5p expression was down-regulated in BC, with a target-regulatory relationship with ESM1 and excellent early cancer screening ability. ESM1 was specifically enriched in lymphatic endothelial cells and participated in BC progression through activation of SPP1 signalling pathway and metabolism-related signalling pathways. Overexpressed ESM1 may mediate a reduced level of immune cell infiltration in TME through immune signalling pathways. ESM1 can be used as a predictive biomarker for immune-related and clinical progression in BC.	bladder
Ureteroenteric repair for strictures after radical cystectomy and urinary diversion: Comparison of the open and robotic approaches.	INTRODUCTION: Ureteroenteric anastomotic stricture (UES) is one of the main complications after radical cystectomy (RC) with urinary diversion, regardless of the surgical approach. The standard surgical treatment for these strictures is usually an open ureteroenteric repair. The use of robotic-assisted surgery is developing as a less invasive alternative. The aim of this study was to compare the results of open and robotic approaches for UES repair. METHODS: A retrospective single-center study was conducted including all patients who underwent ureteroenteric repair for stricture after RC from 2015 to 2024. The primary endpoint was surgical success, defined as the absence of clinical or radiological stricture recurrence at the last follow-up. Complication and stricture recurrence rates were compared between both groups. RESULTS: Twenty-six patients were included: 11 underwent robotic-assisted repair and 15 underwent open repair. No differences between both groups were observed except for the indication of the cystectomy which was more often for oncologic reasons in the open group (80 vs. 36.4%; P=0.04). The median time to UES occurrence was 101 days. The anastomosis used for surgical repair differed significantly in both groups with Bricker being prevalent in the open group (73.3 vs. 9.1%) and side-to-side anastomosis being used only in the robotic group (45.5 vs. 0%; P=0.001). The mean operative time tended to be shorter in the open group but without statistical significance (151.3 vs. 191.8; P=0.15). Conversely the median length of hospital stay tended to be shorter in the robotic group (8 vs. 7 days; P=0.21). The median time to return of bowel function was significantly shorter in the robotic group (3 vs. 2 days; P=0.03). No significant differences were observed in terms of 30-day complication rate (13.3 vs. 27.3%; P=0.62). The success rate of ureteroenteric repair was 100% (P=0.99) in both groups, with a median follow-up of 18.5 months. CONCLUSION: Open and robotic ureteroenteric repair for strictures have a comparable success rate and appears to provide excellent functional results with low morbidity. These results suggest that minimally invasive surgery is a promising alternative, even in patients primary operated in open approach. Larger studies are required to confirm these results.	bladder
Comprehensive analysis of ALYREF gene expression and its correlation with immunotherapy efficacy and circulating tumor cells in bladder cancer.	Bladder cancer (BCa) presents a significant clinical challenge, with a pressing need for biomarkers to predict prognosis and guide immunotherapy. Aly/REF export factor (ALYREF) is a key regulator in various cancers, but its role in bladder cancer (BCa) remains unclear. This study aimed to investigate the clinical significance of ALYREF and its association with immunotherapy response and metastatic potential in BCa. We integrated pan-cancer bioinformatic analyses with clinical validation using RT-qPCR, immunohistochemistry, and Western blot on patient samples. We assessed ALYREF's correlation with clinicopathological features, survival, and response to immune checkpoint inhibitors (ICIs). Circulating tumor cell (CTC) counts were analyzed to link ALYREF to metastatic potential. Functional roles in migration and invasion were validated in vitro using the T24 cell line. ALYREF was significantly upregulated in BCa tissues, correlating with higher tumor grade and poorer overall survival. Paradoxically, high ALYREF expression was also associated with a better response to ICI therapy. Furthermore, elevated ALYREF levels in tumors corresponded to increased CTC counts. In vitro experiments confirmed that ALYREF promotes BCa cell migration and invasion. ALYREF is a dual-role biomarker in BCa. Its overexpression signifies aggressive tumor biology and metastatic risk yet also predicts a favorable response to immunotherapy. ALYREF holds promise for refining patient stratification and personalizing BCa treatment.	bladder
Impact of COVID-19 on Postoperative Complications in Minimal Invasive Radical Cystectomy: A Comprehensive Complication Index-Based Analysis.	PURPOSE: This study aimed to evaluate perioperative outcomes and postoperative complications following minimally invasive radical cystectomy with ileal conduit (RCIC) performed under an enhanced recovery after surgery (ERAS) protocol, using the Clavien-Dindo classification (CDC) and the comprehensive complication index (CCI). METHODS: An ambispective study (2018-2022) was conducted, collecting demographic, perioperative and postoperative data, with a focus on complications among patients treated during and outside the COVID-19 period. Results were compared between surgeries conducted during the COVID-19 pandemic, including the first wave, and those performed in a non-COVID period. RESULTS: Among these 90 patients, 49 underwent surgery during the complete COVID-19 period, compared with 41 patients in the pre- and post-pandemic control period. Additionally, 15 of the cases occurred during the first wave of the pandemic. The COVID-19 group showed a higher rate of pN0 staging (87.8% vs 67.5%, p = 0.021) and fewer pN1 cases (2% vs 20%, p = 0.005) than the control group. The most common complications were genitourinary (71, 78.9%), infectious (59, 65.6%) and gastrointestinal (54, 60%). Median CCI increased significantly with each ascending CDC (r = 0.934, p < 0.001). Notably, 20.3% of patients in CDC ≤3a were reclassified to severe morbidity (CCI ≥33.7), with elevated rates during COVID-19 periods (46.7% and 42.9% vs 34.1%). CCI showed a more consistent correlation with length of stay than CDC (r = 0.551, p < 0.001 vs r = 0.460, p < 0.001). CONCLUSIONS: Minimally invasive RCIC during the COVID-19 pandemic was associated with increased postoperative morbidity. Compared with RCIC, the CCI provides a more accurate estimation of morbidity burden and should be incorporated into standard surgical outcome reporting.	bladder
Effects of a Dendritic Cell Vaccine Loaded With Whole Tumor Antigen on Bladder Cancer Model in hu-PBL-SCID Mice.	The aim of this study was to establish a humanized immune system model in severe combined immunodeficient (SCID) mice, assess dendritic cell (DC) phenotype, and evaluate the therapeutic efficacy of a DC-based vaccine in a bladder cancer model. Bladder cancer was induced in SCID mice by injection of T24 cells, followed by human peripheral blood leukocyte (hu-PBL) inoculation to reconstitute the human immune system. DCs were generated in vitro by culturing hu-PBL for 5 days and matured on the eighth day. The DC vaccine was produced by coculturing with whole tumor antigen which was purified through freezing and melting T24 cells. The therapeutic efficacy of a DC vaccine was evaluated by administering the vaccine to SCID mice at Weeks 5 and 6 after T24 cell injection. Immune reconstitution, phenotype of DCs, tumor weight, and matrix metalloproteinase-7 (MMP-7) mRNA expression were assessed. All SCID mice successfully developed bladder cancer, confirmed as urothelial carcinoma. After hu-PBL inoculation, human IgG was detectable in mouse serum at Week 5, and spleen weight increased over time, indicating successful human immune system reconstitution. Phenotypic analysis of DCs showed high expression of maturation markers, including CD1a (78.07% ± 9.43%), CD80 (60.11% ± 20.50%), and CD83 (46.82% ± 14.15%), indicating functional and mature DCs. Therapeutic intervention with the DC vaccine significantly reduced tumor weight and MMP-7 mRNA expression, with statistical significance (p = 0.0004 for tumor weight and p = 0.0008 for MMP-7). This study successfully established a humanized immune system model in SCID mice and demonstrated that a DC-based vaccine effectively inhibits tumor growth in a bladder cancer model. These results support the potential of DC vaccines as a promising immunotherapeutic strategy for bladder cancer.	bladder
PD-1 and PD-L1 expression in molecular subtypes of muscle-invasive bladder cancer: immunohistochemical characterization and correlation with clinicopathological features.	INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease with variable outcomes, necessitating practical classification systems. Molecular subtyping using immunohistochemical (IHC) markers offers a cost-effective approach for therapeutic guidance and assessing survival. Moreover, MIBC molecular subclassification provides a practical approach for guiding immune checkpoint inhibitor therapy. METHODS: We evaluated 124 MIBC cases using IHC markers GATA3, CK5/6, and p16. Cases were classified as luminal (GATA3+, CK5/6-), basal (GATA3-, CK5/6+), or other (GATA3-, CK5/6-). Luminal cases were further subdivided into luminal unstable (LumU; p16+) and luminal papillary (LumP; p16-). Clinicopathological characteristics of MIBC molecular subtypes were also assessed. PD-1 and PD-L1 expression were evaluated relative to clinicopathological features and MIBC subtypes. RESULTS: In our study, 36.2% of the cases were LumU, 27.6% LumP, and 24.8% basal. The basal subtype generally shows a significantly higher tumor stage (p < 0.05). PD-1 was expressed in 70.5% of cases, with the highest expression in LumU (84.21%). PD-1 expression was significantly higher in the luminal compared to the basal subtype (82.1% vs. 53.8%, p < 0.01). PD-L1, expressed in 40% of cases, was significantly elevated in stage III and considerably higher in basal than luminal subtype (57.7% vs. 34.3%, p < 0.05). CONCLUSION: MIBCs were practically subclassified into LumU, LumP, basal, and other subtypes using three IHC markers. PD-1 expression was higher in the luminal subtype, while PD-L1 was predominantly elevated in the basal subtype. These findings highlight the potential of IHC-based subtyping to guide prognosis and treatment in MIBCs.	bladder
Plasma CAF22 and NfL reflect neuromuscular decline during cisplatin-based chemotherapy and radical cystectomy in muscle-invasive bladder cancer.	BACKGROUND: Cisplatin-based chemotherapy and radical cystectomy are standard treatments for muscle-invasive bladder cancer (MIBC), but their impact on neuromuscular integrity and functional capacity remains elusive. We investigated plasma biomarkers of neuromuscular junction degradation (c-terminal agrin-fragment-22; CAF22) and neuronal injury (Neurofilament light-chain; NfL) in relation to physical capacity in MIBC patients. METHODS: In this prospective study, 42 MIBC patients undergoing neoadjuvant cisplatin-gemcitabine chemotherapy and radical cystectomy were assessed before (T1) and after (T2) chemotherapy, and 4-6 weeks post-surgery (T3). Age- and BMI-matched controls (n = 46) were evaluated once. Plasma CAF22 and NfL were measured alongside handgrip strength (HGS), gait speed (GS), appendicular skeletal muscle index (ASMI), and short physical performance battery (SPPB). RESULTS: Plasma CAF22 and NfL were significantly elevated in patients versus controls at all time points. NfL showed more modest increases in post-treatment. HGS declined from 22.3 ± 3.9 kg at T1 to 17.2 ± 3.3 kg at T3 (p < 0.05), along with reductions in ASMI and GS. Cumulative SPPB scores dropped from 9.02 ± 1.02 to 8.24 ± 1.32. Sarcopenia prevalence rose from 28.5% at T1 to 52.4% at T3. CAF22 was significantly associated with lower HGS and SPPB at T1 (β = - 0.58 and - 0.42, p < 0.001). CAF22 changes correlated with HGS (r = - 0.80) and SPPB (r = - 0.75), while NfL showed weaker but significant correlations. Lab results indicated declines in hemoglobin, albumin, and renal function markers consistent with treatment effects. CONCLUSIONS: CAF22 showed strong associations with treatment-related decline in skeletal muscle, suggesting its potential as an early biomarker of sarcopenia that warrants validation in larger cohorts.	bladder
Real-World Outcomes of Avelumab Maintenance Therapy in Patients With Curatively Unresectable Urothelial Carcinoma in Japan: Results From the Final Analysis of Postmarketing Surveillance.	BACKGROUND: Avelumab maintenance therapy was approved in Japan in February 2021 for the treatment of curatively unresectable urothelial carcinoma (UC) that has not progressed after prior chemotherapy based on results from the JAVELIN Bladder 100 phase 3 trial. We report the final analysis of postmarketing surveillance (PMS) data on the safety and effectiveness of avelumab maintenance in clinical practice in Japan. METHODS: This prospective, multicenter, noninterventional PMS evaluated patients with curatively unresectable UC who received ≥ 1 dose of avelumab maintenance in Japan between February 2021 and December 2021. The observation period was ≤ 52 weeks in all patients. The primary objective was to evaluate the safety of avelumab maintenance based on the occurrence of prespecified adverse drug reactions (ADRs). The secondary objective was to evaluate effectiveness, including time to treatment failure (TTF), time to next-line treatment (TTNT), and overall survival (OS). RESULTS: Data were collected from 453 patients at 213 sites (data cutoff: March 6, 2024). Median age was 73 years, 90.3% had metastatic disease, and prior chemotherapy regimen was gemcitabine + cisplatin in 267 (58.9%), gemcitabine + carboplatin in 163 (36.0%), and others in 23 (5.1%). Any-grade prespecified ADRs occurred in 144 patients (31.8%), including grade ≥ 3 in 35 patients (7.7%). The most common any-grade prespecified ADRs were infusion reaction (11.7%) and thyroid dysfunction (7.3%). Median TTF was 4.6 months (95% CI, 3.8-5.3 months). Median TTNT was 9.9 months (95% CI, 8.3 months-not estimable). OS rates at 6 and 12 months were 89.2% (95% CI, 86.0%-91.8%) and 77.9% (95% CI, 73.7%-81.5%), respectively. CONCLUSION: Final analysis of PMS provides the largest real-world dataset of avelumab maintenance in Japan reported to date. Findings demonstrate the acceptable safety, tolerability, and effectiveness of avelumab maintenance, consistent with data from JAVELIN Bladder 100 and real-world studies in other countries, and support its continued use in clinical practice. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR): UMIN 43435.	bladder
Demonstrating the non-inferiority of robotic radical cystectomy for cT3-cT4 urothelial carcinoma in the era of neoadjuvant chemotherapy: a propensity score-matched analysis.	We evaluated whether robot-assisted radical cystectomy (RARC) is non-inferior to open radical cystectomy (ORC) in patients with cT3-cT4 urothelial carcinoma receiving cisplatin-based neoadjuvant chemotherapy (NAC). We retrospectively analyzed 204 patients (ORC = 123, RARC = 81) across 11 centers. A 1:1 propensity score matching based on age, sex, T stage, and nodal status minimized the selection bias. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared using Kaplan-Meier analyses and log-rank tests. Cox regression identified independent prognostic factors. Before PSM, the RARC group included younger patients and had fewer individuals with cT4 tumors. Following PSM, 81 patients remained in each arm with balanced characteristics. RARC and ORC showed similar RFS (log-rank p = 0.90) and CSS (p = 0.16), whereas OS slightly favored RARC (p = 0.049). In a multivariable analysis, the surgical approach did not independently predict oncologic outcomes; instead, advanced pathologic stage (≥ pT2), lymphovascular invasion, and nodal involvement (≥ N1) were significant risk factors. The operative time was longer, but blood loss was lower in RARC, with no significant difference in positive margins or major complications. RARC demonstrated non-inferior oncologic outcomes compared to ORC in patients with cT3-cT4 urothelial carcinoma treated with NAC. These findings support the feasibility of a minimally invasive approach without compromising efficacy in advanced bladder cancer.	bladder